In 1980, when Zschech was 15, her father rededicated his life to Christ and began taking her to church, where she also became a committed Christian and met her future husband, Mark Zschech. When they married, her husband suggested that they move from Brisbane to Sydney, which was confirmed at a small church they were visiting one Sunday when the guest speaker said in the middle of his sermon, “This doesn’t happen to me very often, but whatever it is you two prayed last night, God says do it now.” They began attending Hills Christian Life Centre, which would become Hillsong Church.

Zschech sang jingles for a number of international companies including McDonald’s, KFC and Coca-Cola, until she eventually joined the staff of Hillsong Church after penning “Shout to the Lord”. She released a vinyl album in 1987 called Make the Choice and a cassette album in 1993 called Pearls & Gold.

Zschech composed “Shout to the Lord” in 1993 and it has become one of the most well-known modern worship songs, being sung by an estimated 25–30 million churchgoers every Sunday since the song’s release. She wrote the song during a time of personal struggle. When she presented it to Hillsong’s then-worship pastor, Geoff Bullock, she was so embarrassed that she requested he face away from her as she played and sang.

“Shout to the Lord” was first recorded on People Just Like Us and has appeared on more than 200 different albums by numerous artists in multiple languages. It is also the title track for the first live album co-produced with Integrity Music featuring Zschech as a worship leader. It was Integrity Music’s first album to feature a female worship leader. The album was nominated for Praise & Worship Album of the Year at the 1997 Dove Awards. The song was nominated in the 1998 Dove Awards’ Song of the Year category. It has been performed for the Pope at the Vatican and for the President of the United States.

Zschech and her husband have three daughters, Amy, Chloe and Zoe. In 2000, she had a miscarriage after 12 weeks.

Shout to the Lord was nominated as Album of the Year for the 1997 Dove Awards and Song of the Year for the 1998 Dove Awards. In 2000, Zschech received a Dove Award nomination for Songwriter of the Year and received the International Award for influence in praise and worship.

In 2003, Zschech released her first official solo album, Kiss of Heaven. Change Your World followed in 2005. She has since released two albums, in 2011, called Simply Darlene and You Are Love. In addition to writing songs, she has written five books: Worship (1996), Extravagant Worship (2002), The Kiss of Heaven (2003), The Great Generational Transition (2009) and Revealing Jesus: A 365-Day Devotional (2013).

On 11 December 2013, Zschech was diagnosed with breast cancer. In a blog dated 30 November 2014, she wrote that she has been healed of cancer, which her doctor termed “quite miraculous”.