The British-based world record holder, who underwent surgery late last year after breaking her elbow in a cycling accident, won comfortably in one minute 6.17 seconds.
"It's great to be here again. It's an absolutely amazing pool and it's always going to be special for me," she told reporters after the first long-course European title of her career.
"I'm happy to post some consistent times, being in hard training still and unrested it's very good for me. Hopefully we can learn some things from this race and carry it out to Rio."
The 19-year-old, who lives in the south-west English city of Plymouth, said the injury had been a big setback in her preparations for the Rio Olympics but the recovery had been faster than expected.
Meilutyte was beaten at the 2015 world championships by Russian Yulia Efimova, currently suspended after testing positive for Meldonium.
In the world champion's absence, Iceland's Hrafnhildu Luthersdottir was her closest rival and took silver with Britain's Chloe Tutton the bronze medallist.
Another 2012 Olympic champion, Ranomi Kromowidjojo of the Netherlands, had to settle for silver in the women's 100 metres freestyle.
Sweden's reigning European champion Sarah Sjoestrom won in 52.82 seconds, a time that would have been good for Olympic gold four years ago, with Kromowidjojo second in 53.24 and team mate Femke Heemskerk taking bronze.
"I hate losing, the Olympics will be a new and a different race and I'm on a good way to Rio," Kromowidjojo said.
World champion Gregorio Paltrinieri of Italy earlier swam the second fastest men's 1,500 metres freestyle of all time to defend his title.
The 21-year-old won in 14:34.04 to shatter his own European record, set at last year's world championships in Russia, by 5.63 seconds.
