Williams, like Federer, 36-years-old but chasing a 24th Slam title, enjoyed a hard-fought 7-5, 6-3 victory over Holland's Arantxa Rus.
At a pre-tournament press conference on Sunday, she said that, far from being a hindrance, motherhood had been a boost to her competitive instinct. Venus, a five-time champion, is No. 9.
On her social-media platforms and in interviews these past months, Williams has spoken frankly about the medical complications she suffered during childbirth and the changes to her body afterward.
She is ranked outside the top 150, but the All England Club made a decision to seed her 25th based on past success, which includes collecting seven of her 23 Grand Slam singles trophies at Wimbledon.
Williams arrived at Wimbledon this week on the heels of a report that she was unhappy at excessive targeting from US Anti-Doping Agency drug testers.
"I didn't realise it was such a discrepancy, at least with the American players".
United States cyclist Taylor Phinney has been tested 90 times by USADA; distance runner Molly Huddle has been tested 74 times, while athlete Galen Rupp has been tested 167 times.
Williams is returning to the grass-court tournament for the first time since 2016 after missing it a year ago while pregnant.
By being seeded 25th, though, Serena is going to likely face no worse than a No. 8 seed in the third round.
"I don't believe there's ever going to be enough testing", Federer said. "How can I have a missed test when it's nowhere near the time I should be there?"
Djokovic, seeded 12th, has been slumping for more than a year and is +650 to win his fourth Wimbledon title. I think I've had seven tests.
French Open chiefs decided against seeding Williams, but Wimbledon officials placed her 25th despite a low ranking of 181 after her maternity absence.
But everything else was familiar for the Swiss star who cruised past world number 57 Lajovic in just 79 minutes.
She added: "I haven't played a tremendous amount of tennis since I had the baby". What I want to know is everyone is getting tested, that we are really working to keep this sport clean.
Then she revved it up, getting to 115 miles per hour in each set.
Being unavailable for tests outside the one-hour window does not count as a missed test.
"I did have a conversation before I knew the information about all the other players", she said.
The Williams siblings aren't playing doubles in this tournament, the way they did at Roland Garros, and that's a good thing for Mom: It gives her more time with her child.
"It's just about being equal and not centering one person out".
"I was like 'I haven't seen Olympia, what am I doing?'. I thought it was very, very noble and honest and cool".
Roger Federer echoed Williams' call for consistent testing when he was asked about Serena's comments later on Sunday.
Having backed up her 2017 U.S. Open triumph by reaching the French Open final last month, Stephens was considered a title hopeful. "Maybe that's the part I don't like so much - the inconsistency of the places where they test", Federer said.