This study examined the effects of prior domain knowledge and learning sequences on learning with concept mapping and hypertext. Participants either made a concept map in a first step and then read the hypertext's contents combined with concept mapping (high activating condition), or they read the hypertext's contents first and then made a concept map and re-read the hypertext's contents (low activating condition). It was hypothesized that the low activating condition would support better learning of relations between concepts for low prior knowledge participants who would need information from hypertext first to efficiently build a map next. For high prior knowledge participants, it was expected that the high activating condition would increase prior knowledge activation that would improve learning by promoting germane cognitive load, or at least would help participants to cope with the cognitive demands of the learning task by reducing extraneous cognitive load. The results confirmed that the low activating condition fostered better learning of relations between the concepts than the high activating condition, regardless of the level of prior knowledge. However, concept mapping behaviors and eye movement data showed that prior knowledge reduced disorientation, improved navigation coherence, and supported better elaboration of semantic relations between the concepts before reading the texts.