The late night host will return for two more years of Chelsea Lately. In addition, she will develop and produce a number of shows though her production shingle Borderline Amazing Prods.
The deal is said to be worth $25 million (£15.8m), according to Deadline.
"Chelsea is an extraordinary talent whose smart, clever, no-holds-barred point of view has clearly been embraced by viewers," said network president Suzanne Kolb.
She continued: "We are thrilled to continue our partnership with Chelsea as we build on the success of Chelsea Lately, which has become the late-night destination for young adults, and collaborate with Borderline Amazing Prods on developing even more hit shows."
Handler added: "It's a great time for women in comedy, and it's a great time to have real breasts."
Handler recently ended her relationship with Andre Balazs after less than one year of dating.
She was previously rumoured to be dating 50 Cent.
Handler lately revealed that she feels confused by female grooming techniques, expressing her displeasure with the new trend of women undergoing anal bleaching.