Alf Wight (the real James Herriot) initially stipulated that all the incidents in the TV series had to be closely based on those in his books. By the end of Season 3, all of Wight's books had been televised, and it was thought that the series would have to end. However producer Bill Sellars persuaded Wight to let the scriptwriters devise new stories as long as the scripts were approved by him and remained faithful to the spirit of his books.

Cringley House, the building in Askrigg that was used as the filming location for the exterior of Skeldale House, was for many years a home for vulnerable adults. However new owners opened it as a bed-and-breakfast and tea-room on 23 March 2013. Jim Wight, son of Alf Wight (aka James Herriot) was due to perform the opening ceremony but was unable to attend because the roads to Askrigg were blocked by heavy snow. The building was renamed Skeldale House in honour of its connection with the programme.

Robert Hardy had problems with the writers in the later seasons of the show in that they seemed to be inserting scenes in every episode where Siegfried Farnon would lose his temper and "blow up" to comic effect. Hardy had to fight with the writers to give Siegfried the dimensions and depth of character he felt he'd had in the show's early seasons.

Christopher Timothy was originally offered the part of Tristan Farnon but he said he would only appear if he could play James Herriot.

Siegfried Farnon's dogs actually belonged to Robert Hardy, the actor who played him, which explains why they behaved so naturally around him.

During the filming of the second series (shown September-December 1978), Christopher Timothy broke his leg in a car crash. Some of the storylines had to be altered to explain why James Herriot was walking with a limp, or spent most of his time in the surgery rather than going out to farms to treat animals.

During the first three seasons of the show, Christopher Timothy and Carol Drinkwater, who played James and Helen Herriot, had an off-screen relationship. Although the relationship ended amicably, Drinkwater decided not to return to the show when it was revived for Seasons 4-7. Her part was re-cast, with Lynda Bellingham as Helen.

The programme was known colloquially and humourously as "All Creatures Grunt and Smell".

Peter Davison's role in the series led directly to him being cast as the Fifth Doctor in Doctor Who (1963), because Doctor Who (1963) producer John Nathan-Turner had worked with him when he was the production unit manager on this series.

Christopher Timothy has said that he suffered badly from typecasting in television after starring in the enormously popular series. For years afterwards, he found many of his offers of work were for very similar roles and he became seen as a "vet" actor, which also frustrated his agent.

The TV sets for the Skeldale House surgery are now on display at "The World of James Herriot," a museum in Thirsk, North Yorkshire, England, which is located in the house where the real James Herriot had his surgery.

For the first few episodes of Season 5, Helen was bedridden with a slipped disc to hide Lynda Bellingham's pregnancy.

According to an interview with Peter Davison, an episode was rehearsed for ten days.

The character of Siegfried was based on a real-life vet called Donald Sinclair. By a remarkable coincidence, the character of Basil Fawlty in Fawlty Towers (1975) was also based on a real-life hotelier called Donald Sinclair.

Christopher Timothy, Robert Hardy, Peter Davison and Carol Drinkwater all shared memories for the book "All Memories Great & Small", published as part of the centenary celebrations for James Herriot in 2016. Other interviewees sharing their memories of making the series, many for the first time, include actors Andrea Gibb (Deirdre McEwan), Jean Heywood (Mrs Alton), Ali Lewis (Rosie Herriot), Peter Alexander (St. John), Lois Baxter (Margery Egerton), Paul Clayton (Brian Weeting), Fine Time Fontayne (George Forsyth/Joe Bentley), Gillian Hanna (Betty Sanders), Derek Hicks (Willie Bannister), Pete Ivatts (Mr. Blackburn/Tom Maxwell), Vivien Keene (Mary Trenholm), Ray Mangion (Franco Pedretti), Norman Mann (Richard Edmundson), Nicholas McArdle (Mr. Worley), Joanna McCallum (Lady Hulton), Elizabeth Millbank (Alice McTavish), Suzanne Neve (Joan Clifford), Jonathan Owen (Peter Gillard), David Quilter (Andrew Bruce), Pamela Salem (Zoe Bennett), Jessica Sewell (Mary Clarke), Madeline Smith (Angela Farmer/Anne Grantley), Amanda Waring (Elizabeth Rayner) and Susan Wooldridge (Daughter of Margaretta Scott). From behind the scenes, the interviewees are Bob Blagden (Director), Sandy Byrne (Widow of Writer Johnny Byrne), Alex Christison (Film Sound), Carol Churchill (Make-up Designer), David Crozier (Designer), Nigel Curzon (Designer), Roger Davenport (Writer), Rowena Dean (Make-up Artist), Mike Duxbury (Film Editor), Paul Finch (Son of Writer Brian Finch), Graham Frake (Lighting Cameraman), Roderick Graham (Director), Joyce Hawkins (Costume Designer), Terry Hodgkinson (Writer), June Hudson (Costume Designer), David Hughes (Sound), William Humble (Writer), Brian Jones (Gaffer), Peter Loring (Film Cameraman), Richard Martin (Director), Christopher Penfold (Script Editor/Writer), Les Podraza (Scene Hand), Janice Rider (Costume Designer), Tony Redston (Production Associate), Michael Russell (Writer), Helen Scarsbrook (Wardrobe), Bill Sellars (Producer), Pip Short (Grip/AFM/Location Manager), Sam Snape (Writer), Maggie Thomas (Make-up Artist), David Tilley (Assistant Floor Manager), Tony Virgo (Director) and John Williams (Film Cameraman). Written by Oliver Crocker and published by Miwk.

Peter Davison didn't like the director Terence Dudley and claimed on a Doctor Who (1963) DVD commentary (for "Planet of Fire") that he has only ever once lost his temper on a programme, which was during an episode of "All Creatures Great and Small", directed by Dudley, in which he thought Dudley was doing a sloppy job and not taking it seriously.