Victory saw the sixth-seeded Russian go one better on England's south coast after she was beaten in the 2023 final at Devonshire Park by Madison Keys -- who lost to Fernandez in the semi-finals of this year's Wimbledon warm-up event.
In defeating former US Open finalist Fernandez, world number 14 Kasatkina won her seventh career title and first since 2022 following three previous defeats in finals this season.
"It's been a year, but it feels like it's been a few days since last year when I was standing here," said the 27-year-old. "It was a tough battle today. It's been a long road to the title but I am really proud."
Kasatkina now heads to Wimbledon, where she is seeded 14th, to play China's Zhang Shuai in the first round of the women's singles, with the tournament starting on Monday.
Fernandez's serve was broken in the first game and Kasatkina backed that up by holding her own serve.
A gruelling fifth game of 11 deuces, which lasted just over 20 minutes, including a stoppage while a spectator received medical treatment, saw Fernandez force three break points.
Nevertheless, Kasatkina held and stayed ahead before clinching the set with a second break in the ninth game after the 21-year-old Canadian double-faulted.
Kasatkina, who knocked out Britain's Emma Raducanu in the quarter-finals, then surged into a 3-0 lead in the second set.
But Fernandez, defeated by Raducanu in the 2021 US Open final, fought back to 3-3 and then broke Kasatkina for the second time in the set as the Russian double-faulted.
Fernandez now led 4-3 only for Kasatkina to break back immediately.
With Fernandez's confidence dented, Kasatkina stayed ahead and won the match when her opponent overhit a forehand.
Fernandez, however, was happy with her week's work after reaching her first grass-court final.
"It's a beautiful tournament at Eastbourne and I enjoyed my time here. Hopefully we have many more of these finals," Fernandez said.
"My team have pushed me the past couple of months and the hard work is paying off so now we have to keep going, working and never give up."
