In the absence of her great rival, the Australian Ariarne Titmus, who dispossessed her of her world record over the distance a month ago, the American rocket won in 3 min 58.15.
She leads 15-year-old Canadian Summer McIntosh (3:59.39) and another American, Leah Smith (4:02.08).
Ledecky had reigned in the 400m freestyle at the 2013, 2015 and 2017 Worlds before being dethroned in 2019 by Titmus, who also deprived her of Olympic gold in Tokyo last summer.
The 25-year-old swimmer can aim for the individual treble in the Hungarian capital's Duna Arena: she is also the favorite to win the 800m and 1,500m.
© 2022 AFP