In 2000 the Coronation Street producers wanted her to perform a storyline involving Natalie having a miscarriage, but she refused, saying the character had already lost her husband and son.However Welch, who was expecting a baby the same year, decided to leave the serial in 2000.Of her casting, Welch stated: “I’m so thrilled to be part of such an iconic show; it’s so exciting!I have several friends on the show and it’s a great crowd so I can’t wait to get started.At the time, Welch commented, "I am looking forward to being a mum again and spending some time with my baby and am relishing the prospect of new challenges in my career." A spokesperson for Granada TV commented "The character [Natalie] will not be killed off and the door will be left open for her possible return.We wish Denise well both for the birth of her baby and for her future career." In 2002 Welch guest-starred in ITV's Where the Heart Is, and BBC's hospital drama Holby City, playing risk manager Pam Mc Grath who conducted an on-screen relationship with the character Mubbs Hussein (played by Ian Aspinall).In 2001, he appeared on Lily Savage's Blankety Blank.Since 2005 she has been a regular panellist on ITV's topical lunchtime chat show Loose Women.
She is known for her roles as Natalie Barnes in Coronation Street (1997–2000) and Steph Haydock in Waterloo Road (2006–2010).
She has guest-starred twice in ITV's long-running police drama The Bill (1997; 2006) and has also appeared in BBC's Doctors (2004); Down to Earth (2004–2005); Born and Bred (2002–2003); starred (second billing) in the British feature film The Jealous God (2005); and starred in Hollyoaks: In the City (2006) among others.
From 2006 to 2010 she appeared as French teacher Steph Haydock in the successful BBC school-based drama series Waterloo Road, and played Janet Gold (Goldie) in an episode called "Rogue" of the long-running programme, Casualty, which aired on 2 July 2011.
Welch originally won the role as Frances Myers in Bad Girls, but ended up declining it owing to illness at the time; her future Waterloo Road co-star Eva Pope received the part instead.
Welch left Waterloo Road and intended not to return for Series 6, but eventually decided to return for the final two episodes.