A high quality science education in primary and secondary schools contributes to developing scientific literacy and would be expected to predispose students to study the enabling sciences at university. The major purpose of this study was to assess the practice and problems in science laboratory activities in the secondary school of Wolaita Zone, Southern Nations, Nationalities and People's Region. This study was conducted in five government secondary schools from three Town administrative and two Woreda administrative from Wolaita Zone. The Woreda education offices and secondary schools were selected by purposive sampling techniques based on the proximity. The secondary school teachers were selected by systematic sampling techniques while principals, vice principals and Woreda education supervisor expert were selected purposely. Primary data were gathered from 114 teachers, 8 laboratory technicians, 10 principals and 235 students by questionnaire, interview and observation and secondary data were collected from documents such as annual plans and laboratory reports, annual reports. The data gathered through questionnaires were analyzed using percentages and mean. The findings of this study indicated that: (i) The current status of laboratory works in secondary schools of Wolaita Zones is in a very low level where science teaching learning process is not supported adequately by laboratory works; (ii) The most determinant constraints of laboratory activities in secondary schools include lack of laboratory rooms, inadequate supply of lab equipments, reagents and facilities, absence of trained laboratory technicians/teachers, lack of commitment and interest of teachers, lack of regular schedule for laboratory activities, poor management, monitoring and evaluations of laboratory activities, no system for grading and assessment of laboratory examinations; and (iii) laboratory activities did not get the necessary concern in all schools investigated by this study. Therefore, to bring the progress of laboratory activities in schools and to play a great role in initiating and supporting science teaching in the class, there should awareness creation by all stakeholders of the education system. Current and regular workshops and short term training's about laboratory activities should be given to science teachers in order to enhance and update their laboratory skills and capacities to carry out experiments and demonstrations more effectively and efficiently. The respondents agreed that the government should give special consideration and effective implementation strategies for the improvement and efficient ways of science teaching in schools in order to achieve the mission and goals of the new education policy.