The film was released in the United States on Kumail Nanjiani and Emily V. Gordon's tenth wedding anniversary.

Kumail Nanjiani and Adeel Akhtar are the only two actors in their on-screen family of actual Pakistani origin. The rest of the actors (Anupam Kher, Zenobia Shroff and Shenaz Treasury) are all Indian.

Kumail Nanjiani personally contacted Anupam Kher about taking the role of his father, Azmat. Kher accepted the role after learning that Nanjiani's real father personally expressed a desire for him to take the role.

While writing the script, Kumail Nanjiani wanted his on-screen family to reflect the jokey and humorous traits of his real-life family. He bemoaned that so many Muslim characters were so frequently depicted as overly serious, and he aimed to avoid that stereotype.

The film premiered at the Sundance Film Festival where it was very well received, which started a bidding war between Sony, Focus Features, Amazon and Netflix for the distribution rights. The co-creator of the film, Kumail Nanjiani, wanted the film to have theatrical distribution, which eliminated Netflix from the bidding war since they are not a proponent in that distribution model. The film's distribution rights were eventually bought for around $12 million by Amazon, who is a big proponent of the theatrical experience, with all of its films getting at least some kind of theatrical run. The $12 million deal was one of the largest deals in Sundance's history.

The decision to add the real-life photos of Emily and Kumail in the credits was suggested by actress Leslie Mann after seeing an early cut of the film.

While searching for funding, the producers submitted the script to a variety of potential studios. Within three hours of submission, FilmNation made an offer to fund the whole movie, no strings attached.

The screenplay for The Big Sick (2017) was written by Emily V. Gordon and her husband Kumail Nanjiani, and it was loosely based on the real-life courtship between them before their marriage in 2007. According to Nanjiani, the idea to make a script about them was first inspired by the film's eventual co-producer, Judd Apatow, when the two met while appearing in a 2012 episode of the "You Made It Weird" podcast. Developed over the course of three years, the script was called semi-autobiographical because, in addition to the two lead characters modeled after them, many of the events occurring during Gordon and Nanjiani's relationship were noted as being portrayed to an extent in the film. Though not part of the original script, a real-life incident involving Holly Hunter heckling an unnamed player during a U.S. Open tennis match inspired a similar scene in the film where Nanjiani's character is heckled during one of his stand-up sets.

Writer Emily V. Gordon mentioned that her real-life parents are quite different than their on-screen depiction.

In the film, it is mentioned more than once that Kumail Nanjiani is a fan of the TV series The X-Files (1993). In reality, Kumail Nanjiani actually appeared in an episode of The X-Files (1993) in 2016.

Producer Judd Apatow reached out to Ray Romano for the part of Terry, after briefly working with him in the movie Funny People (2009). He was also a huge fan of Romano's sitcom Everybody Loves Raymond (1996).

The line where Terry mentions the game "Throw the Chalk at Jimmy" was improvised by Ray Romano.

Holly Hunter came up with the idea of having her and Zoe Kazan wearing the same necklace to imply the strong mother/daughter bond between the two characters.

In November 2016, Kumail Nanjiani was a guest on the NPR podcast "Pop Culture Happy Hour." When one of the podcast's hosts, Linda Holmes, invited him to plug his upcoming movie (which at the time was still filming), he said, "My wife and I wrote a movie and I'm in it, and it's going to come out next year. Right now it's called 'The Big Sick,' but the name's going to change. So just look for the rom-com about a brown man and a white woman, starring me."

Kumail Nanjiani was both excited and nervous about writing the script. Five years had passed since his wife Emily V. Gordon's health scare, but the feelings from the experience were still fresh in his mind.

Kumail Nanjiani and Emily V. Gordon spent three years writing the film's script. They would frequently receive notes and suggestions from producers Judd Apatow and Barry Mendel.

Before auditioning, actress Zoe Kazan watched videos of Kumail Nanjiani and Emily V. Gordon to help get a better understanding of them and their characters.

Holly Hunter would rearrange props on set to help her get into character.

Kumail Nanjiani played a version of himself in the film, including having the same name. However, his wife, Emily V. Gordon, had her name changed to "Emily Gardner."

Director Michael Showalter commented on the second act's darker (though still humorous) tone after Emily goes into her coma. He referred to how the movie approaches life, stating, "No matter how bad a situation gets, you've got to have humor."

In a hospital scene, Emily's wristband briefly shows her date of birth, May 5. This is the real birthday of Emily V. Gordon, alhough different years.

The Big Sick (2017) was Kumail Nanjiani's first lead role in a feature film.

The film was the only non-Best Picture nominee for the year to be nominated for Best Original Screenplay at the Oscars.

Kumail Nanjiani's real-life wife, writer Emily V. Gordon, stood in for actress Zoe Kazan in one pivotal hospital scene, as seen on The IMDb Show (2017).

When CJ (Bo Burnham) was doing stand-up comedy, the audience's reactions were all natural, as Bo Burnham did not use them in rehearsal.

Emily and her mother wear the same necklace through most of the film. It is a gold pendant that has a sun on one side, with the word "love" engraved on the other side.

Composer Michael Andrews initially incorporated Eastern-style music into his score to help illustrate the film's themes of culture clash and assimilation. This idea was eventually scrapped as Andrews said it "felt forced."

Kumail Nanjiani and Emily V. Gordon had a podcast called The Indoor Kids where they discussed video games. The name refers to a line from Wet Hot American Summer (2001) which director Michael Showalter co-wrote.

While directing the film, Michael Showalter frequently collaborated with the cast and encouraged improvisation.

Producer Judd Apatow was attracted to the project because, aside from it being funny, it tackled a variety of topics and themes including relationships, religion, family and stability.

Mary's stand-up routine with the flip-chart easel is based on Aidy Bryant's real stand-up routine.

Rehearsals for the film were nearly delayed when actor Anupam Kher was unable to travel from Mumbai, India to New York, due to an issue with his visa. Fortunately, the problem was quickly resolved and production commenced as scheduled.

In a nod to the fact that both the character of Kumail and the real-life Kumail Nanjiani are fans of the television series The X-Files (1993), in this movie, Kumail's cellphone ringtone is the "Theme from The X-Files" by Mark Snow.

In the film, Kumail's sister-in-law suggests he should be on Saturday Night Live (1975). Aidy Bryant, who played Mary, is a cast member of Saturday Night Live (1975).

This was the opening night film for the 2017 Seattle International Film Festival.

Production on the film began on May 11, 2016 in New York City.

Composer Michael Andrews had worked with producer Judd Apatow before on the films Bridesmaids (2011) and Funny People (2009) as well as the shows Undeclared (2001) and Freaks and Geeks (1999).

Kumail Nanjiani had previously worked with director Michael Showalter in the film Hello, My Name Is Doris (2015).

The film was shown on the closing night of the 3rd Edition (2017) of "IndieBo" (Bogota's Independent Film Festival) as part of the "In Focus" section.

In an interview on The Late Show, Zoe Kazan admitted that while filming the scenes where she was in a coma she often fell asleep and inevitably ruined takes by waking up in the middle of them.

Emily V. Gordon: co-writer and the "real" Emily can be seen in the last scene of the film in the comedy club sitting near CJ and Mary.

In this movie, when the character of Kumail finally tells his parents that he is (1) in love with Emily; (2) Emily is not Pakistani; and (3) Emily is very (maybe mortally) ill, Kumail's mother immediately shuns him (telling him "you are not my son") and remains quite angry with him for the duration of the movie, only showing a small sign of thawing at the very end of the movie. During an "All Things Considered" interview with the real Kumail Nanjiani and his real-life wife and co-screenwriter, Emily V. Gordon, Nanjiani said that this scene was one way in which his real life was very different from its depiction in this movie--that in reality, when his mother first heard about Emily and her serious illness, she was very concerned and supportive, and it was only once Emily was out of the coma and it was clear that she would recover that Mrs. Nanjiani expressed her anger at Kumail for dating a white woman and for only pretending to be amenable to an arranged marriage to a Pakistani woman. Gordon added that in their real lives, Kumail's mother "never, never once, never came close to her disowning" Kumail.

The fight between Emily and Kumail, when Emily discovers the pictures of Pakistani women in Kumail's room, never happened in real life. The real Emily, however, did recall how tension had arisen between the two after Kumail wouldn't introduce her to his family.

Co-writer Emily V. Gordon revealed in an interview with Empire magazine that one of the most difficult scenes to write was the one where it's revealed that Terry (Ray Romano) had an affair. This didn't occur in real life, and was suggested by producer Judd Apatow. Gordon found it very hard to discuss this subplot with her real parents.