This experimental study aimed to replicate and extend a previous efficacy study of an elementary grade content literacy intervention that demonstrated positive effects on students' vocabulary knowledge depth, argumentative writing, and reading comprehension. Using a cluster (school) randomized trial design, this replication experiment was conducted with 5,494 first- and second-grade students in 30 elementary schools in an urban school district located in the southeastern USA. Teachers implemented thematic lessons (20 lessons) that provided an intellectual framework for helping students who acquire networks of related vocabulary knowledge while learning science and social studies content. Teachers integrated thematic lessons, concept mapping, and interactive read-alouds of conceptually related informational texts to enable their students to build networks of vocabulary knowledge and to transfer this knowledge to argumentative writing and collaborative research activities. Confirmatory analyses replicated positive findings on science vocabulary knowledge depth (ES = 0.50) and argumentative writing (ES = 0.24) and also extended positive findings to social studies vocabulary knowledge depth (ES = 0.56) and argumentative writing (ES = 0.44). Positive and statistically significant findings were not replicated on domain-general reading comprehension. Exploratory analyses indicated that students' vocabulary knowledge depth partially mediated the impact of content literacy instruction on domain-specific argumentative writing outcomes.