What happens in the first week of school could very well set the stage for the rest of the school year. Setting high standards for science activities based in inquiry can start on the first day of science class and develop as the year unfolds. With the use of simple, readily available, inexpensive materials, an efficient mystery box lesson can be a first-week hit that sets the bar for the rest of the year. Children love the challenge of mystery boxes. Unknown objects are placed in boxes that children explore with their senses. The mystery is to discover what is in the boxes by observing and describing clues. This guided inquiry activity promotes collaboration and acts as a natural icebreaker between the students and the teacher. Although the authors have used this with third-, fifth-, and seventh-grade students, it is easily adapted to grade levels 1-8. As an open-ended activity, this lesson gives teachers the opportunity to assess the students' attitudes and prior knowledge of science, as well as their skills. The high level of peer-interaction required in this lesson promotes language acquisition and is well suited for English language learners. Since there are no right or wrong answers, students are challenged to go beyond the content level by explaining the rationale behind their predictions and defending their guesses. This lesson addresses the scientific and engineering practices recommended in "A Framework for K-12 Science Education: Practices, crosscutting concepts, and core ideas" of engaging in argument from evidence, constructing explanations, and analyzing and interpreting data. (Contains 1 online resource.)