Serena Williams struggled initially on her return to action at the AEGON International, coming from a set down to beat Tsvetana Pironkova.
Making her first competitive appearance since winning Wimbledon last year, former world number one Williams battled past Bulgarian Pironkova 1-6 6-3 6-4 in two hours and four minutes on Tuesday.
Granted a wildcard for the Eastbourne event, the 29-year-old American now faces a second-round match against top seed Vera Zvonareva as she continues her comeback from foot surgery and blood clots.
Russian Zvonareva set up the headline clash with 13-time Grand Slam winner Williams by defeating Briton Heather Watson 6-3 6-3.
In other first-round matches at the Devonshire Park Lawn Tennis Club, fourth seed Francesca Schiavone of Italy beat Estonian Kaia Kanepi 7-6 (9-7) 6-1.
Schiavone will now meet Poland's Agnieszka Radwanska.
Elena Baltacha made light work of France's Aravane Rezai with a 6-2 6-1 victory in their first round encounter, but the wildcard Briton must next tackle third seed Victoria Azarenka.
Qualifier Bojana Jovanovski ousted Russian Anastasia Pavlyuchenkova 7-6 (11-9) 6-4 to book a second-round match against seventh seed Australian Samantha Stosur.
Fellow qualifier Mirjana Lucic was less successful, losing to Russian Ekaterina Makarova 6-1 3-6 6-4.
Makarova will face fifth seed Czech Petra Kvitova in the second round.
Marion Bartoli of France, seeded sixth, saw off Czech Lucie Safarova 6-3 3-6 7-6 (9-7) and will now play Spaniard Maria Jose Martinez Sanchez.
Finally, Serbian Ana Ivanovic defeated German Julia Goerges 6-4 6-3, setting up a second-round match against fellow former world number one Venus Williams.