The 35-year-old, who last week announced her engagement, defeated France's Pauline Parmentier 6-3 6-4.
Williams had been on the sidelines with shoulder and knee problems since the US Open semi-finals in September.
"You always feel rusty for your first match," she said. "But mentally I knew how to get it back and get in there."
Williams had to wait an extra day to make her first appearance of 2017 after rain forced the postponement of her first-round match on Monday.
She took 74 minutes to beat the world number 69, serving eight aces, including one on match point, but also four double-faults in the swirling wind.
"It was so windy out there," she added. "You really have to be ready to move your feet, so I went to what my coach told me and I was like 'you know how to play in the wind, you've done it many times before' so I just tried to adjust to it.''
Williams will next face compatriot Madison Brengle, the world number 74.
World number two Serena Williams made a successful return after almost four months out as she won her first-round match at the ASB Classic in Auckland.