Clarke, one of America's best-known death penalty experts, will make an opening statement and present witnesses in the penalty phase of the trial that will see Tsarnaev sentenced to death or life in prison.
The April 15, 2013 double bombing killed three people and wounded 264 others in one of the deadliest attacks in the United States since 9/11.
Tsarnaev was convicted on all 30 counts this month by the 12-person jury that will now determine his fate: execution or life without parole.
He was scared of and manipulated by his radical, older brother Tamerlan, 26, the true mastermind of the attacks, they will argue.
More From This Section
Tamerlan was shot dead by police while the pair were on the run.
If anyone can get Tsarnaev off the death penalty, experts believe it is Clarke, in her early 60s, and a tireless opponent of capital punishment.
"That's her speciality," said Robert Bloom, professor at Boston College Law School. "She knows how to do it, she is possibly the best lawyer in the country (for that)," he added.
She knows how to humanise her clients. She unmasks their sufferings, and their social and family backgrounds. She does not excuse but she seeks to understand and to explain.
"None of us, including those accused of crime, wants to be defined by the worst moment, or worst day of our lives," she told the magazine of the Washington and Lee University School of Law, where she taught, in 2010.