The general rule is that on’yomi is for compound words
and kun’yomi is for stand-alone kanji words
and words with okurigana
to be born
but there are many exceptions. You can definitely start to guess the readings of words with a good accuracy once you know the most common on’yomi and kun’yomi readings for a kanji, but really you need to learn the words to be sure. Because of that, it’s not really worth it to try and learn all the readings of a kanji before learning the vocab, so WK only asks you to remember one or two of the most common readings when you learn the kanji. If you have trouble with specific kanji such as 人 (じん vs にん) there are threads on here where people have attempted to find patterns.
Rendaku is also a thing which takes some getting used to.